title: Synthesis and investigation of dihydroxychalcones as calpain and cathepsin inhibitors.
abstract: In order to identify potential calpain and cathepsin inhibitors we prepared 12 dihydroxychalcone analogues and tested their ability to inhibit μ-calpain, m-calpain, cathepsins B and L. In the calpain inhibition test, compound 10 exhibited the most active inhibitory activity against m-calpain with an IC50 value of 25.25±0.901μM. With respect to inhibition of cathepsins B and L, compound 13 exhibited the most potent inhibitory activity on cathepsin L and moderate inhibitory activity on cathepsin B with IC50 values of 2.80±0.100 and 11.47±0.087μM, respectively. Our results suggest the possibility of developing dual calpain and cathepsin inhibitors by properly modulating structures and/or combining the essential aspects of the functional group effective for specific calpain and cathepsin inhibition.
authors.affiliation: College of Pharmacy, Graduate School of Pharmaceutical Sciences, Global Top5 Research Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Kyung Hye
authors.initials: KH
authors.lastname: Baek
authors.forename: Radha
authors.initials: R
authors.lastname: Karki
authors.forename: Eung-Seok
authors.initials: ES
authors.lastname: Lee
authors.forename: Younghwa
authors.initials: Y
authors.lastname: Na
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Kwon
mesh_terms: D002154:Calpain / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D047188:Chalcones; D011480:Protease Inhibitors; D002403:Cathepsins; D002154:Calpain
keywords: Calpain inhibitor; Cathepsin B; Dihydroxychalcone; L Inhibitor